The neuropathological phenotype of prion disease is one of the two most commonly used biological parameters used to identify and define prion strains and to characterize the effects of PrP constructs in transgenic mice. The Neuropathology ore provides a neurohistological and immunohistochemical service to the projects, however, it has also made significant contributions to understanding the etiology and pathogenesis of prion diseases. The Aims of the Neuropathology Core are: (1) To sacrifice animals, remove organs, and free or embed tissue blocks in preparation for a variety of morphological studies; (2) To perform classical neurohistological staining and immunohistochemical staining procedures on aldehyde-fixed tissue sections to evaluate the degree of vacuolar degeneration (hematoxylin and eosin stain), to search for amyloid plaques (PAS and CONGO red stains), to evaluate nerve cell loss (Luxol fast blue-PAS stain), and to evaluate the degree of astrocytic gliosis (glial fibrillary acidic protein immunostain); (2) To localize PrP/sc in aldehyde fixed tissue sections pretreated by the hydrolytic autoclaving technique; (3) To localize and quantify PrP/c and PrP/sc in frozen brain sections by the histoblot technique; (4) To fix peripheral nerve in glutaraldehyde, embed in araldite plastic, and prepare toluidine blue stained sections in selected animals to search for possible peripheral neuropathies; (5) To quantify the degree of songiform degeneration, reactive astrocytic gliosis, and PrP/c accumulation by computer-assisted morphometry; (6) To maintain a data base for storage and retrieval of the now several thousand animals which have been processed in part by the Neuropathology Core of this Program Project, as well as, by other Neuropathology Cores which have been part of other prion disease program projects; and (7) To consult with and prepare photomicrographs and graphs to project investigators for publication.